Four-component regio-divergent carbonylative condensations for the sustainable syntheses of acylhydrazones

Abstract

Catalytic carbonylation, which converts multiple green or sustainable starting materials to critical compounds with high atom-economy and chemoselectivity, is a highly desirable and elusive process. Furthermore, carbonylations of alkenes with hydrazines are performed to produce acylhydrazones, which are versatile building blocks for the formation of numerous pharmaceuticals. However, the syntheses of functionalized acylhydrazones involve multi-step reactions that require harsh conditions. Therefore, we herein report practical one-pot catalytic hydrohydrazono-carbonylation condensations of alkenes with hydrazines and aldehydes to form acylhydrazones, with water as the sole coproduct, overcoming the challenge of regioselectivity in multicomponent reactions. Using appropriate ligands, branched or linear N-alkyl-substituted acylhydrazones may be obtained in good-to-high yields with excellent regioselectivities. All the acylhydrazone derivatives are unknown compounds and gram-scale (255.8 g) acylhydrazones are prepared using this protocol, and a possible reaction mechanism is proposed based on control experiments and labeling studies.